Endophthalmitis W. David
Caused
Irvine, MD; Harry W. Flynn, Jr, MD;
The medical records of 52 patients (53 eyes) with culture-proven gram\x=req-\ negative endophthalmitis between January 1982 and December 1990 were reviewed. Pseudomonas aeruginosa (23% [12/53]) and Haemophilus influenzae(19% [10/53]) were the most frequent isolates in this series. Overall, 26 (49%) of 53 treated patients achieved 20/400 or better visual acuity. Fifty-two (98%) of the original 53 gram-negative isolates were sensitive to the aminoglycoside antibiotics. To determine their sensitivity to recently developed antibiotics, 35 of the isolates were again grown on culture media and their sensitivities to ceftazidime, ciprofloxacin, and imipenem were obtained. Only ceftazidime demonstrated in vitro efficacy for all the organisms tested. \s=b\
(Arch Ophthalmol. 1992;110:1450-1454)
"Dacterial endophthalmitis remains an
-*-' uncommon but devastating compli¬ cation of ocular surgery, trauma, and systemic infections. Although the most common causative organisms are the
gram-positive category, gram-negative organisms have been isolated in 15% to 29% of cases of clinical endophthalmitis in the larger reported series.15 In gen¬ eral, endophthalmitis caused by gramnegative organisms has been associated with poor visual outcomes despite prompt treatment with intraocular an¬ tibiotics and often with vitrectomy.3·4 The purpose of this report is to re¬ view culture-proven gram-negative en¬ dophthalmitis in a large series of pa¬ tients to determine the following: (1)
for publication April 2, 1992. From the Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami (Fla) School of Medicine. Reprint requests to Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, PO Box 016880, Miami, FL 33101 (Dr Flynn).
Accepted
Darlene
by Gram-negative Organisms Miller, MT, MA; Stephen C. Pflugfelder,
the relative frequency of gram-negative
endophthalmitis institution, (2) frequency of each gramnegative organism, (3) the relative fre¬ quency of the various etiologies, (4) the at
our
the relative
antibiotic sensitivities, and (5) the vi¬ sual outcomes after treatment. SUBJECTS AND METHODS We reviewed the clinical records in the
microbiology laboratory of the Bascom Palmer Eye Institute, University of Miami (Fla) School of Medicine, to identify cases of culture-proven gram-negative endoph¬ thalmitis treated between January 1982 and December 1990. Gram-negative isolates were
present in 62 (18.5%) of 336
cases
of
culture-proven endophthalmitis. Of 62 cases identified, nine were excluded for a variety of reasons, including lost medical records (three), advanced endophthalmitis requiring primary evisceration (three), patient's men¬ tal status precluding adequate visual assess¬
(two), and mixed flora isolated from culture with the predominant organisms be¬ ing staphylococci (one). The remaining 53 cases form the basis of this report. All 53 of the patients had clinical examina¬ tions, diagnostic procedures to obtain in¬ traocular fluid for culture, and treatment performed at the Bascom Palmer Eye Insti¬ tute. Cultures were obtained from both the vitreous and anterior chamber in 33 cases. Nineteen cases had vitreous cultures alone, and only one case had anterior chamber cul¬ ture alone. In the 33 cases that had simulta¬ neous vitreous and anterior chamber cul¬ tures, both were positive in 21 cases (64%). In nine (27%) of the 33 cases, the vitreous cultures were positive with negative ante¬ rior chamber cultures, and in three (9.1%) the anterior chamber cultures were positive with negative vitreous cultures. The criteria for positive cultures in endophthalmitis es¬ tablished by the Infection Control Commit¬ tee at our institution were met in all 53 cases and included one of the following: (1) growth of the same organism on two or more culture media or (2) semiconfluent growth on one or more solid media at the inoculation site. The results of antibiotic sensitivity tests performed at the time of the original diagment
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MD
reviewed for all 53 sensitivity of the gram-negative organisms in this series to more recently developed antibiotics, all available isolates were again grown on cul¬ ture media, and minimal inhibitory concen¬ trations were obtained by automated tube dilution tests (Vitek, St Louis, Mo) as well as nostic cases.
procedure
were
To determine the
Kirby-Bauer sensitivities to ceftazidime, cip¬ rofloxacin, and imipenem. All patients were treated with intraocular antibiotics. Fifty (94%) of the 53 patients were initially treated with intraocular injec¬ tion of an aminoglycoside antibiotic. Fortysix (87%) also received intraocular vancomycin
hydrochloride
or
cefazolin.
Forty-five
(85%) received periocular antibiotics during their initial treatment. Forty-six (87%) were
treated with topical antibiotic drops and 44 (83%) received intravenous antibiotics as part of their initial treatment. Ten (19%) re¬ ceived intraocular dexamethasone phos¬ phate together with intraocular antibiotics at the initial intervention. An initial three-port pars plana vitrec¬ tomy was performed in 10 (19%) of the 53 cases. A limited two-port (infusion line and vitrectomy instrument) or anterior vitrec¬ tomy was performed in an additional 13 cases (25%). The remaining 30 cases (57%) had di¬ agnostic anterior chamber and/or vitreous needle aspirations before the injection of in¬ traocular antibiotics. The decision to per¬ form vitrectomy was made by the individual treating physician and was not based on a
randomized, prospective protocol. The follow-up period ranged from 1 week to 86 months, with a mean of 11.75 months.
A follow-up period of only 1 week was avail¬ able for cases that rapidly progressed to evisceration or enucleation. To be consistent with previous endophthalmitis reports, the cases were divided into two visual outcome groups based on better than or equal to 20/ 400 visual acuity compared with cases with final visual acuity less than 20/400. RESULTS
Species Identified The relative frequency of isolation of the various gram-negative organisms is given in Table 1. Many different species
Table
1.—Gram-negative
Organism_Postoperative
Bacteria Bleb
Pseudomonas aeruginosa Other Pseudomonas species Haemophilus influenzae Proteus species Serratia marcescens
Causing Endophthalmitis Trauma 1
in Various
Suture Removal
Etiologic Categories* Corneal
0
31
(8.3) (100.0) (80.0) 5/07 (71.4) 2/05 (40.0) 1/04 (25.0) 1/04 (25.0) 1/03 (33.3) 1/02 (50.0) 1/01 (100.0) 1/01 (100.0) 26/53(49.1)
identified, with Pseudomonas aeruginosa (12/53 [23%]) being the most common. Other Pseudomonas species
isolates included Pseudomonas maltophilia, Pseudomonas cepacia, Pseudo¬ monas stutzeri, and Pseudomonas
paucimobilis. Haemophilus influenzae
cultured in 10 (19%) of the 53 cases, and Proteus species were isolated in seven (13%). The other gram-negative species were less common and are noted in Table 1. was
Etiology The clinical
settings in which gramnegative endophthalmitis occurred are summarized in Table 1. Postoperative endophthalmitis was the most common of infection (31/53 [58%]). The 31
postoperative cases included 26 extracapsular cataract extractions with or without intraocular lens implantation, three cases of secondary intraocular lens, and two penetrating keratoplasties. Twenty-four (77%) of the 31 post¬ operative cases had acute onset (within 1
week),
and all acute
cases
occurred
following cataract surgery. Seven cases were classified as subacute or delayed onset (diagnosis made from 3 weeks to 7 months after the procedure). The su¬ bacute or delayed-onset group included the three cases of secondary intraocular lens, the two cases of penetrating kera¬ toplasty, and two cataract extractions with intraocular lens implantation. Four of these
subacute or had predisposing factors identified that included suture abscesses in the two cases of penetrat¬ ing keratoplasty, vitreous to the limbal wound in one case of cataract extrac¬ tion, and an exposed scierai fixation su¬ ture in one of the cases of secondary in¬ traocular lens. The organisms involved in these cases included Haemophilus influenzae (three), Serratia mar¬ cescens (one), aeruginosa (one), Kleb-
delayed-onset
8
previous conjunctival filtering bleb; trauma, previous penetrating ocular injury.
were
cause
20 400.
1/12
_
*Bleb indicates
Acuity
4/04 8/10
Morganella morganii Citrobacter diversus Escherichia coli Klebsieila pneumoniae Enterobacter cloacae Moraxella nonliquefaciens Total
Visual
Endogenous_Ulcer_No. (%)_
seven
cases
siella pneumoniae mobilis (one).
(one), and
Conjunctival filtering
ciated
pauci-
aminoglycoside antibiotics. Pseudo¬ cepacia was the only organism
monas
bleb-asso¬
endophthalmitis accounted for
eight (15%) of the 53 cases. These cases included glaucoma filtering blebs as
well as inadvertent blebs in cataract wounds. Haemophilus influenzae was isolated in six (75%) of the eight blebassociated cases. The time between the initial operative procedure and the on¬ set of the endophthalmitis ranged from 1 week to 12 years. Trauma preceded the onset of gramnegative endophthalmitis in five cases (9.4%). There were four cases involving penetrating trauma and one case of blunt trauma with rupture of a cataract wound. Suture removal was associated with the onset of endophthalmitis in four (7.5%) of the 53 cases. Two cases in¬ volved removal of penetrating kerato¬ plasty sutures, and two cases followed removal of cataract wound sutures. In three cases, endophthalmitis was diag¬ nosed within 48 hours after suture re¬ moval. The remaining case was diag¬ nosed 14 days following removal of a keratoplasty suture, and Proteus vulgaris was the organism isolated.
Endogenous endophthalmitis
oc¬
curred in three eyes of two patients. Escherichia coli was isolated from all three eyes. One patient had urosepsis, with urine and blood cultures also pos¬ itive for E coli. The second patient had a history of both cirrhosis and renal failure, and E coli was also isolated from blood cultures. Perforated corneal ulcers caused by aeruginosa accounted for two (3.8%) of the 53 cases. Table 1 provides a sum¬ mary of the various organisms found in each etiologic category. Antibiotic Sensitivities
Fifty-two (98%) of the 53 gramnegative isolates were sensitive to the
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that demonstrated in vitro resistance aminoglycosides. This organ¬ ism was sensitive to chloramphenicol, piperacillin, and trimethoprimsulfamethoxazole. Thirty-five (66%) of the 53 original gram-negative isolates were frozen and were capable of being regrown on cul¬ ture media. Sensitivity patterns to ceftazidime, ciprofloxacin, and imipenem as well as repeated sensitivities to the aminoglycosides were obtained in these 35 isolates (Table 2). All 35 or¬ to all the
ganisms, including cepacia, were sen¬ sitive to ceftazidime. Pseudomonas
ce¬
pacia remained resistant to all the aminoglycosides as well as imipenem and ciprofloxacin. The 10 aeruginosa isolates were sensitive to all the antibi¬ otics tested, with the exception of one isolate, which was found to be resistant
to
imipenem.
Visual Outcome
The eyes in this study were divided into two visual outcome groups based on final visual acuity (eyes with visual acuity better than or equal to 20/400 compared with eyes with less than 20/ 400) in Tables 3 and 4. These visual acuity results are also presented as a function of etiologic category, infecting organism, and method of treatment. Overall, 49% (26/53) of eyes recovered a visual acuity of 20/400 or better. This percentage includes 15% (8/53) achiev¬ ing 20/50 or better visual acuity. Nine¬ teen cases (36%) ended with no light perception or had enucleation or evis¬ ceration. Of the 31 eyes in which gram-
negative endophthalmitis developed postoperatively, 13 (42%) achieved 20/ 400 or better visual acuity (Table 3). Six (75%) of eight conjunctival filtering
bleb-associated cases and three (60%) of
Table
Organism Pseudomonas aeruginosa Pseudomonas cepacia
No. Tested 10
Pseudomonas stützen Pseudomonas maltophilia Pseudomonas paucimobilis Proteus mirabilis Haemophilus influenzae Serratia marcescens Citrobacter diversus
35
%'
Amikacin
Sulfate
Gentamicin 100
100
100 100
100 100 100 100
Morganella morganii Escherichia coll Klebsiella pneumoniae Total
2.—Gram-negative Organism Sensitivities,
100 100 100
100 100 100 100 100 100 97
100 100 100 100 100 97
Tobramycin 100 100 100 100 100 100 100 100 100 100 100 97
Ceftazidime 100
100 100 100 100 100 100 100 100 100 100 100 100
Ciprofloxacin
Imipenem
100
90
100 100
100
100 100 100 100 100 100 100 94
100 100 100 100 100 100 100 100 91
(34/35) (35/35) (33/35) (32/35) »Sensitivities were defined by minimal inhibitory concentration and disk diffusion techniques. These organisms were frozen after the initial cultures and were ca¬ pable of being grown again on culture media for sensitivity testing. (34/35)
(No.)
(34/35)
Table 3.—Posttreatment Visual Acuity for Various
Etiologic Categories
Categories_Total, No. (%)_a20/400 Acuity, No. (%) Postoperative_31 (58.5)_13/31 (41.9)_ Etiologic
Conjunctival filtering,
bleb associated
8(15.1)
6/8(75.0)
Trauma_5 (9.4)_3/5 (60.0)_ Suture removal_4 (7.5)_3/4 (75.0)_ Endogenous_3 (5.7)_1/3 (33.3)_ Perforated corneal ulcer_2 (3.8)_0/2 (0.0)_ 53(100.0)
Total
cases of traumatic gram-negative endophthalmitis regained this level of visual acuity. One (33%) of three endog¬
five
and neither of two corneal ulcer-related cases recovered 20/400 or better visual acuity. Pseudomonas aeruginosa, the most enous cases
common
gram-negative endophthalmi¬
tis isolate, was associated with a poor visual prognosis, since only one of 12 eyes recovered 20/400 or better vision (Table 4). In contrast to aeruginosa, all four eyes infected with other Pseudomonas species achieved 20/400 or better vision. Other gram-negative cases achieving this level of visual re¬ influenzae (8/10 covery included [80%]) and Proteus species (5/7 [71%]). Eyes that were initially treated with vitrectomy (either three-port pars plana vitrectomy or two-port anterior vitrectomy) and intraocular antibiotics achieved 20/400 or better in 15 (65%) of 23 cases. The eyes that underwent ini¬ tial anterior chamber and/or vitreous aspiration and intraocular antibiotics recovered 20/400 or better vision in 11 (37%) of 30 cases (Table 4). Ten eyes in this series received in¬ traocular dexamethasone phosphate (0.4 mg) together with intraocular anti¬ biotics at the initial treatment. Seven of these patients achieved 20/400 or better visual acuity. Pseudomonas aerugi-
26/53(49.1)
the organism responsible for endophthalmitis in three eyes receiving nosa was
intraocular dexamethasone, and one of these eyes achieved a final visual acuity of 20/300. A repeat injection of intraocular an¬ tibiotics was performed in 24 of the 53 cases in this series (Table 5). Nineteen of these 24 cases had a repeat culture performed, and 14 of these 19 had pos¬ itive culture results. All 14 cases had the same isolate as the original organ¬ ism identified. Eleven of these 14 cases had initial vitreous aspiration and three had initial vitrectomy. Seven of the 24 cases achieved 20/400 or better visual acuity at the last follow-up examination. Persistent infection as manifested by a repeat positive culture occurred in 13% (3/23) of the group with initial vitrec¬ tomy and 37% (11/30) of the group with initial vitreous aspiration. Of the 10 cases receiving intraocular dexametha¬ sone phosphate (0.4 mg), one case had a persistent positive intraocular culture for Serratia marcescens. This case re¬ ceived a repeat injection of intraocular antibiotics and achieved 20/200 visual
acuity. Complications
After Treatment
Because this report is a retrospective chart review, the accurate determina¬ tion of antibiotic toxicity is difficult.
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Prospective fundus photography or fluorescein angiography was not per¬ formed for all patients. However, no description of macular whitening or presumed macular infarction was re¬
corded in the medical record. Retinal detachment was observed within 1 month of the initial treatment in three cases. One eye had successful repair of retinal detachment using pars plana vitrectomy, fluid air exchange, endolaser treatment, and scierai buck¬ ling procedure. The final visual acuity in this eye was 20/70. The remaining two eyes ended with no light perception, with recurrent retinal detachment. COMMENT
Of 336 cases of culture-proven bacte¬ rial endophthalmitis in our laboratory during the 8-year period reviewed, 62 (18.5%) were due to gram-negative iso¬ lates. This percentage is consistent with
recently reported endophthalmitis
se¬
ries from other institutions, in which the incidence of gram-negative endoph¬ thalmitis ranged from 15% to 18%.:!"5 In previous reports from our institution, gram-negative organisms have been cultured in up to 29% of the cases of bacterial endophthalmitis.1,2 Pseudo¬ monas aeruginosa, the most common organism in this report, accounted for 12 (23%) of the 53 cases. This relative frequency of aeruginosa is consistent with a previous report from our institu¬ tion in 1980, in which aeruginosa oc¬ curred in five (22%) of 23 gram-negative endophthalmitis isolates.2 The visual acuity outcomes from aeruginosa endophthalmitis in the current series were poor, since only one of 12 eyes achieved 20/400 or better visual acuity. The one case with a more favorable outcome was a postoperative case ini¬ tially treated with pars plana vitree-
Table 4.—Method of Treatment for
Gram-negative Endophthalmitis Compared Part A
PPV
Organism
With
Specific Organisms Part B
(VA, £20/400) Tap
Ant Vit
PPV
and Final Visual Outcome*
(VA, 20/400* I-
No. Initial Procedure
Culture
Reinjected
No. Recultured
11
24
14 19
Vitrectomy Vitreous aspiration Total
14
The numerator gives the number of eyes with 20/400 the total number of eyes in the category.
tomy and administration of 1 mg of in¬ traocular vancomycin hydrochloride,
0.1 mg of tobramycin, and 0.4 mg of dexamethasone phosphate. This patient achieved a final visual acuity of 20/300. Eight of the remaining 11 eyes pro¬ gressed to no light perception vision, and seven eyes eventually were evis¬ cerated or enucleated. In previous re¬ ports in which final visual acuities were
reported by organism, aeruginosa endophthalmitis has also been associ¬ ated with a poor visual outcome, with five (83%) of six eyes progressing to no light perception visual acuity and the
remaining eye achieving only counting fingers visual acuity.3·5"7 The virulence of aeruginosa in causing severe infections is believed to be multifactoral.8·3 Pseudomonas aeruginosa exists in two forms, a freely
motile form and a microcolony form en¬ cased in a glycocalyx. Organism motility is important in the establishment of infection. In addition, the glycocalyx aeruginosa organism protects the against antibiotic penetration and often prevents phagocytosis. Once estab¬
lished,
aeruginosa produces
a num¬
ber of toxins and proteases that cause host cell destruction and secondarily increase the invasiveness of the organ¬ ism. Finally, aeruginosa does produce ß-lactamase, which renders many com-
or
better visual
Culture
I
Culture
2/3
1/2
1/11 3/14
2/3 3/5
acuity and the denominator gives
monly used antibiotics ineffective against the organism.9 Although aeruginosa is by far the most commonly isolated species of the genus causing infection, other pseudomonads are occasionally oppor¬ tunistic pathogens, and their antimicro¬ bial susceptibility patterns frequently differ from that oî aeruginosa.'3 These Pseudomonas species were isolated in four of our 53 cases. Three of these cases were secondary to penetrat¬ ing ocular trauma, and the remaining case occurred after cataract extraction. All four cases were associated with re¬ covery of useful vision ranging from 20/20 to 20/200. Pseudomonas cepacia was the only organism isolated in this series that was resistant to all of the aminoglycoside antibiotics. In that case,
infrequent
endophthalmitis was diagnosed 12 days after repair of a scierai laceration. Ini¬ tial management included three-port pars plana vitrectomy and intraocular injection of 1 mg of vancomycin hydro¬ chloride and 0.1 mg of gentamicin sul¬ fate. Postoperatively, the intraocular inflammation persisted, and subse¬ quently, after antibiotics sensitivities
intraocular chloramwith clearing of the infection and a return of 20/20 visual were
obtained,
phenicol was injected,
acuity. Haemophilus influenzae was the sec-
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Tap.
needle
53
aspiration of intraocular fluid (all
ond most common organism isolated and accounted for 10 (19%) of the 53 cases. Overall, H influenzae cases achieved 20/400 or better visual acuity in eight (80%) of 10 cases. Haemophilus influenzae was cultured in all three of the cases of secondary intraocular lens in which gram-negative endophthalmi¬ tis developed, and all three recovered vision of 20/400 or better. Six (60%) of the 10 Haemophilus isolates were in conjunctival filtering bleb-associated cases. In bleb-associated Haemophilus endophthalmitis cases, 20/400 or better visual acuity was achieved in four (67%) of six cases. In the largest previously reported study of bleb-associated en¬ dophthalmitis, Mandelbaum and associ¬ ates7 from our institution described H influenzae in seven (70%) of their 10 gram-negative cases. Three cases from this previous report are included in our series of 53 cases. In previous endophthalmitis series from other institutions, Proteus species had been cultured with a frequency ranging from 11% to 40% of the gramnegative isolates.3"5·10 In these reports, Proteus was found most commonly in the acute postoperative setting and was generally associated with a poor visual outcome. Proteus species were isolated in seven (13%) of our 53 cases, and five (71%) of the seven cases recovered vision ranging from 20/30 to 20/200. The relative frequency (Table 1) of the etio¬ logic categories for these cases of gramnegative endophthalmitis does not ap¬ pear significantly different from previous endophthalmitis reports.2·3 In a previous study2 from our institution reporting the etiology of culture-proven bacterial endophthalmitis, 55.9% of cases followed intraocular surgery, 20.5% were in association with conjunc¬ tival filtering blebs, 19.1% occurred af¬ ter trauma, and 4.4% were endogenous.2
Puliafito and associates3 described etio¬
logic categories with similar percentages
in their review of 36 consecutive cases. Nine cases of gram-negative endoph¬ thalmitis following ocular trauma have been described, and three (33%) of these cases achieved 20/400 or better visual acuity.3·5·1114 Proteus mirabilis, K pneumoniae, and the Enterobacter species were generally associated with poorer visual outcomes in these reports. In our series, three (60%) of the five posttraumatic cases recovered 20/400 or better vi¬ sual acuity. The organisms in the current report associated with better vision in¬ cluded cepacia, maltophilia, and stützen. Pseudomonas aeruginosa and Proteus mirabilis, the remaining two isolates from traumatic cases in our se¬ ries, were associated with final visual acuities of no light perception. The enteric gram-negative organ¬ isms are a relatively common cause of endogenous bacterial endophthalmitis. Most reported cases occur in association with urinary or gastrointestinal tract in¬ fection. Escherichia coli endophthalmi¬ tis generally carries a poor visual prog¬ nosis, since no previously reported cases have achieved 20/400 or better visual
acuity.1517 Endogenous endophthalmitis secondary to E coli accounted for three of our 53 cases. One patient with bilateral E coli endophthalmitis retained 20/200 vi¬ sual acuity in one eye while the other eye progressed to no light perception. Both eyes were treated with diagnostic vitre¬ ous aspiration and intraocular antibiot¬ ics; however, there was a 4-day delay in treating the second eye, which pro¬ gressed to no light perception visual acu¬ ity. In another patient with unilateral in-
fection, the final visual acuity was also no light perception. The role of vitrectomy in the treat¬ ment of endophthalmitis is controver¬ sial and is being investigated in the En¬ dophthalmitis Vitrectomy Study.18 Many physicians prefer vitrectomy in the initial treatment of all endoph¬
thalmitis cases, whereas others reserve vitrectomy for the eyes with more se¬ vere inflammation. In this retrospec¬ tive review of gram-negative cases, eyes generally presented with severe inflammation, no view of the posterior pole details, and visual acuity of hand motions or worse. The individual physi¬ cian made the decision to use or not to use vitrectomy in the current series. Although the vitrectomy decision was not based on a prospective protocol, it is interesting to note that 65% (15/23) of the vitrectomy-treated eyes compared with 37% (11/30) of the vitreous aspiration-treated eyes achieved 20/ 400 or better visual acuity. The currently generally recom¬ mended intraocular antibiotic regimen for endophthalmitis includes vancomycin plus an aminoglycoside.19 This com¬ bination provides broad coverage against a broad spectrum of grampositive and gram-negative organisms. The aminoglycosides have been consid¬ ered the drugs of choice for gramnegative infections, and they continue to provide excellent gram-negative cov¬ erage.20 In our series, only one (P cepa¬ cia) of 53 gram-negative isolates dem¬ onstrated in vitro resistance to the aminoglycosides. Despite their efficacy, the routine use of aminoglycosides for endophthalmitis treatment and prophy-
Iaxis has recently been questioned be¬ cause of inconsistent coverage of grampositive organisms and potential retinal toxic reaction.21 Other antibiotics in¬ cluding ceftazidime, ciprofloxacin, and imipenem have been suggested as pos¬ sible alternatives to the aminoglyco¬ sides, and preliminary toxicity reports suggest that these agents may be safe for intraocular injection.2225 Of these al¬ ternatives, our data suggest that ceftazidime may be the most promising, since all gram-negative isolates tested were found to be sensitive to this anti¬ biotic. A clinical report has shown a successful treatment outcome with the use of intraocular vancomycin, ceftazi¬ dime, and dexamethasone.25 We believe that ceftazidime may replace the ami¬ noglycosides as the drug of choice in the treatment and prophylaxis of gram-
negative endophthalmitis. The
use
of intraocular dexametha¬
during the initial treatment of en¬ dophthalmitis in these cases did not ap¬ pear to potentiate the infection or have sone
adverse influence on the final visual result. Seven of 10 eyes receiving in¬ traocular dexamethasone in addition to intraocular antibiotics achieved 20/400 or better vision. Although the data from the current series do not prove a bene¬ ficial effect from the use of intraocular steroids, our clinical impression is that intraocular steroids decrease intraocu¬ lar inflammation and speed visual re¬ covery. We currently administer in¬ traocular dexamethasone phosphate (0.4 mg) together with broad-spectrum intraocular antibiotics in the initial treatment of suspected bacterial en¬ an
dophthalmitis.
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92:387-392. 7. Mandelbaum S, Forster RK, Gelender H, Culbertson W. Late onset endophthalmitis associated with filtering blebs. Ophthalmology. 1985;92: 964-972. 8. Stratton CW, Tausk F. Intrinsic resistance of Pseudomonas aeruginosa. Antibiot Chemother.
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18. Doft BH. The endophthalmitis vitrectomy study. Arch Ophthalmol. 1991;109:487-489. 19. Flynn HW Jr, Pflugfelder SC, Culbertson WW, Davis JL. Recognition, treatment, and prevention of endophthalmitis. Semin Ophthalmol.
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20. Sanford JP. Guide to Antimicrobial Therapy. West Bethesda, Md: Antimicrobial Therapy Inc; 1991:39. 21. Campochiaro PA, Conway BP. Aminoglycoside toxicity: a survey of retinal specialists: implications for ocular use. Arch Ophthalmol. 1991;109: 946-950. 22. Jay WM, Fishman P, Aziz M, Shockley RK. Intravitreal ceftazidime in a rabbit model: dose- and time-dependent toxicity and pharmacokinetic analysis. J Ocul Pharmacol. 1987;3:257\x=req-\ 262. 23. Stevens SX, Fouraker BD, Jensen HG, Intraocular safety of ciprofloxacin. Arch Ophthalmol.
1991;109:1737-1743. 24. Derick RJ, Paylor R, Peyman GA. Toxicity of
imipenem in vitreous replacement fluid. Ann Ophthalmol. 1987;19:338-339. 25. Stonecipher KG, Parmley VC, Jensen H, Rowsey JJ. Infectious endophthalmitis following sutureless cataract surgery. Arch Ophthalmol. 1991;109:1562-1563.
Caused
Irvine, MD; Harry W. Flynn, Jr, MD;
The medical records of 52 patients (53 eyes) with culture-proven gram\x=req-\ negative endophthalmitis between January 1982 and December 1990 were reviewed. Pseudomonas aeruginosa (23% [12/53]) and Haemophilus influenzae(19% [10/53]) were the most frequent isolates in this series. Overall, 26 (49%) of 53 treated patients achieved 20/400 or better visual acuity. Fifty-two (98%) of the original 53 gram-negative isolates were sensitive to the aminoglycoside antibiotics. To determine their sensitivity to recently developed antibiotics, 35 of the isolates were again grown on culture media and their sensitivities to ceftazidime, ciprofloxacin, and imipenem were obtained. Only ceftazidime demonstrated in vitro efficacy for all the organisms tested. \s=b\
(Arch Ophthalmol. 1992;110:1450-1454)
"Dacterial endophthalmitis remains an
-*-' uncommon but devastating compli¬ cation of ocular surgery, trauma, and systemic infections. Although the most common causative organisms are the
gram-positive category, gram-negative organisms have been isolated in 15% to 29% of cases of clinical endophthalmitis in the larger reported series.15 In gen¬ eral, endophthalmitis caused by gramnegative organisms has been associated with poor visual outcomes despite prompt treatment with intraocular an¬ tibiotics and often with vitrectomy.3·4 The purpose of this report is to re¬ view culture-proven gram-negative en¬ dophthalmitis in a large series of pa¬ tients to determine the following: (1)
for publication April 2, 1992. From the Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami (Fla) School of Medicine. Reprint requests to Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, PO Box 016880, Miami, FL 33101 (Dr Flynn).
Accepted
Darlene
by Gram-negative Organisms Miller, MT, MA; Stephen C. Pflugfelder,
the relative frequency of gram-negative
endophthalmitis institution, (2) frequency of each gramnegative organism, (3) the relative fre¬ quency of the various etiologies, (4) the at
our
the relative
antibiotic sensitivities, and (5) the vi¬ sual outcomes after treatment. SUBJECTS AND METHODS We reviewed the clinical records in the
microbiology laboratory of the Bascom Palmer Eye Institute, University of Miami (Fla) School of Medicine, to identify cases of culture-proven gram-negative endoph¬ thalmitis treated between January 1982 and December 1990. Gram-negative isolates were
present in 62 (18.5%) of 336
cases
of
culture-proven endophthalmitis. Of 62 cases identified, nine were excluded for a variety of reasons, including lost medical records (three), advanced endophthalmitis requiring primary evisceration (three), patient's men¬ tal status precluding adequate visual assess¬
(two), and mixed flora isolated from culture with the predominant organisms be¬ ing staphylococci (one). The remaining 53 cases form the basis of this report. All 53 of the patients had clinical examina¬ tions, diagnostic procedures to obtain in¬ traocular fluid for culture, and treatment performed at the Bascom Palmer Eye Insti¬ tute. Cultures were obtained from both the vitreous and anterior chamber in 33 cases. Nineteen cases had vitreous cultures alone, and only one case had anterior chamber cul¬ ture alone. In the 33 cases that had simulta¬ neous vitreous and anterior chamber cul¬ tures, both were positive in 21 cases (64%). In nine (27%) of the 33 cases, the vitreous cultures were positive with negative ante¬ rior chamber cultures, and in three (9.1%) the anterior chamber cultures were positive with negative vitreous cultures. The criteria for positive cultures in endophthalmitis es¬ tablished by the Infection Control Commit¬ tee at our institution were met in all 53 cases and included one of the following: (1) growth of the same organism on two or more culture media or (2) semiconfluent growth on one or more solid media at the inoculation site. The results of antibiotic sensitivity tests performed at the time of the original diagment
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MD
reviewed for all 53 sensitivity of the gram-negative organisms in this series to more recently developed antibiotics, all available isolates were again grown on cul¬ ture media, and minimal inhibitory concen¬ trations were obtained by automated tube dilution tests (Vitek, St Louis, Mo) as well as nostic cases.
procedure
were
To determine the
Kirby-Bauer sensitivities to ceftazidime, cip¬ rofloxacin, and imipenem. All patients were treated with intraocular antibiotics. Fifty (94%) of the 53 patients were initially treated with intraocular injec¬ tion of an aminoglycoside antibiotic. Fortysix (87%) also received intraocular vancomycin
hydrochloride
or
cefazolin.
Forty-five
(85%) received periocular antibiotics during their initial treatment. Forty-six (87%) were
treated with topical antibiotic drops and 44 (83%) received intravenous antibiotics as part of their initial treatment. Ten (19%) re¬ ceived intraocular dexamethasone phos¬ phate together with intraocular antibiotics at the initial intervention. An initial three-port pars plana vitrec¬ tomy was performed in 10 (19%) of the 53 cases. A limited two-port (infusion line and vitrectomy instrument) or anterior vitrec¬ tomy was performed in an additional 13 cases (25%). The remaining 30 cases (57%) had di¬ agnostic anterior chamber and/or vitreous needle aspirations before the injection of in¬ traocular antibiotics. The decision to per¬ form vitrectomy was made by the individual treating physician and was not based on a
randomized, prospective protocol. The follow-up period ranged from 1 week to 86 months, with a mean of 11.75 months.
A follow-up period of only 1 week was avail¬ able for cases that rapidly progressed to evisceration or enucleation. To be consistent with previous endophthalmitis reports, the cases were divided into two visual outcome groups based on better than or equal to 20/ 400 visual acuity compared with cases with final visual acuity less than 20/400. RESULTS
Species Identified The relative frequency of isolation of the various gram-negative organisms is given in Table 1. Many different species
Table
1.—Gram-negative
Organism_Postoperative
Bacteria Bleb
Pseudomonas aeruginosa Other Pseudomonas species Haemophilus influenzae Proteus species Serratia marcescens
Causing Endophthalmitis Trauma 1
in Various
Suture Removal
Etiologic Categories* Corneal
0
31
(8.3) (100.0) (80.0) 5/07 (71.4) 2/05 (40.0) 1/04 (25.0) 1/04 (25.0) 1/03 (33.3) 1/02 (50.0) 1/01 (100.0) 1/01 (100.0) 26/53(49.1)
identified, with Pseudomonas aeruginosa (12/53 [23%]) being the most common. Other Pseudomonas species
isolates included Pseudomonas maltophilia, Pseudomonas cepacia, Pseudo¬ monas stutzeri, and Pseudomonas
paucimobilis. Haemophilus influenzae
cultured in 10 (19%) of the 53 cases, and Proteus species were isolated in seven (13%). The other gram-negative species were less common and are noted in Table 1. was
Etiology The clinical
settings in which gramnegative endophthalmitis occurred are summarized in Table 1. Postoperative endophthalmitis was the most common of infection (31/53 [58%]). The 31
postoperative cases included 26 extracapsular cataract extractions with or without intraocular lens implantation, three cases of secondary intraocular lens, and two penetrating keratoplasties. Twenty-four (77%) of the 31 post¬ operative cases had acute onset (within 1
week),
and all acute
cases
occurred
following cataract surgery. Seven cases were classified as subacute or delayed onset (diagnosis made from 3 weeks to 7 months after the procedure). The su¬ bacute or delayed-onset group included the three cases of secondary intraocular lens, the two cases of penetrating kera¬ toplasty, and two cataract extractions with intraocular lens implantation. Four of these
subacute or had predisposing factors identified that included suture abscesses in the two cases of penetrat¬ ing keratoplasty, vitreous to the limbal wound in one case of cataract extrac¬ tion, and an exposed scierai fixation su¬ ture in one of the cases of secondary in¬ traocular lens. The organisms involved in these cases included Haemophilus influenzae (three), Serratia mar¬ cescens (one), aeruginosa (one), Kleb-
delayed-onset
8
previous conjunctival filtering bleb; trauma, previous penetrating ocular injury.
were
cause
20 400.
1/12
_
*Bleb indicates
Acuity
4/04 8/10
Morganella morganii Citrobacter diversus Escherichia coli Klebsieila pneumoniae Enterobacter cloacae Moraxella nonliquefaciens Total
Visual
Endogenous_Ulcer_No. (%)_
seven
cases
siella pneumoniae mobilis (one).
(one), and
Conjunctival filtering
ciated
pauci-
aminoglycoside antibiotics. Pseudo¬ cepacia was the only organism
monas
bleb-asso¬
endophthalmitis accounted for
eight (15%) of the 53 cases. These cases included glaucoma filtering blebs as
well as inadvertent blebs in cataract wounds. Haemophilus influenzae was isolated in six (75%) of the eight blebassociated cases. The time between the initial operative procedure and the on¬ set of the endophthalmitis ranged from 1 week to 12 years. Trauma preceded the onset of gramnegative endophthalmitis in five cases (9.4%). There were four cases involving penetrating trauma and one case of blunt trauma with rupture of a cataract wound. Suture removal was associated with the onset of endophthalmitis in four (7.5%) of the 53 cases. Two cases in¬ volved removal of penetrating kerato¬ plasty sutures, and two cases followed removal of cataract wound sutures. In three cases, endophthalmitis was diag¬ nosed within 48 hours after suture re¬ moval. The remaining case was diag¬ nosed 14 days following removal of a keratoplasty suture, and Proteus vulgaris was the organism isolated.
Endogenous endophthalmitis
oc¬
curred in three eyes of two patients. Escherichia coli was isolated from all three eyes. One patient had urosepsis, with urine and blood cultures also pos¬ itive for E coli. The second patient had a history of both cirrhosis and renal failure, and E coli was also isolated from blood cultures. Perforated corneal ulcers caused by aeruginosa accounted for two (3.8%) of the 53 cases. Table 1 provides a sum¬ mary of the various organisms found in each etiologic category. Antibiotic Sensitivities
Fifty-two (98%) of the 53 gramnegative isolates were sensitive to the
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that demonstrated in vitro resistance aminoglycosides. This organ¬ ism was sensitive to chloramphenicol, piperacillin, and trimethoprimsulfamethoxazole. Thirty-five (66%) of the 53 original gram-negative isolates were frozen and were capable of being regrown on cul¬ ture media. Sensitivity patterns to ceftazidime, ciprofloxacin, and imipenem as well as repeated sensitivities to the aminoglycosides were obtained in these 35 isolates (Table 2). All 35 or¬ to all the
ganisms, including cepacia, were sen¬ sitive to ceftazidime. Pseudomonas
ce¬
pacia remained resistant to all the aminoglycosides as well as imipenem and ciprofloxacin. The 10 aeruginosa isolates were sensitive to all the antibi¬ otics tested, with the exception of one isolate, which was found to be resistant
to
imipenem.
Visual Outcome
The eyes in this study were divided into two visual outcome groups based on final visual acuity (eyes with visual acuity better than or equal to 20/400 compared with eyes with less than 20/ 400) in Tables 3 and 4. These visual acuity results are also presented as a function of etiologic category, infecting organism, and method of treatment. Overall, 49% (26/53) of eyes recovered a visual acuity of 20/400 or better. This percentage includes 15% (8/53) achiev¬ ing 20/50 or better visual acuity. Nine¬ teen cases (36%) ended with no light perception or had enucleation or evis¬ ceration. Of the 31 eyes in which gram-
negative endophthalmitis developed postoperatively, 13 (42%) achieved 20/ 400 or better visual acuity (Table 3). Six (75%) of eight conjunctival filtering
bleb-associated cases and three (60%) of
Table
Organism Pseudomonas aeruginosa Pseudomonas cepacia
No. Tested 10
Pseudomonas stützen Pseudomonas maltophilia Pseudomonas paucimobilis Proteus mirabilis Haemophilus influenzae Serratia marcescens Citrobacter diversus
35
%'
Amikacin
Sulfate
Gentamicin 100
100
100 100
100 100 100 100
Morganella morganii Escherichia coll Klebsiella pneumoniae Total
2.—Gram-negative Organism Sensitivities,
100 100 100
100 100 100 100 100 100 97
100 100 100 100 100 97
Tobramycin 100 100 100 100 100 100 100 100 100 100 100 97
Ceftazidime 100
100 100 100 100 100 100 100 100 100 100 100 100
Ciprofloxacin
Imipenem
100
90
100 100
100
100 100 100 100 100 100 100 94
100 100 100 100 100 100 100 100 91
(34/35) (35/35) (33/35) (32/35) »Sensitivities were defined by minimal inhibitory concentration and disk diffusion techniques. These organisms were frozen after the initial cultures and were ca¬ pable of being grown again on culture media for sensitivity testing. (34/35)
(No.)
(34/35)
Table 3.—Posttreatment Visual Acuity for Various
Etiologic Categories
Categories_Total, No. (%)_a20/400 Acuity, No. (%) Postoperative_31 (58.5)_13/31 (41.9)_ Etiologic
Conjunctival filtering,
bleb associated
8(15.1)
6/8(75.0)
Trauma_5 (9.4)_3/5 (60.0)_ Suture removal_4 (7.5)_3/4 (75.0)_ Endogenous_3 (5.7)_1/3 (33.3)_ Perforated corneal ulcer_2 (3.8)_0/2 (0.0)_ 53(100.0)
Total
cases of traumatic gram-negative endophthalmitis regained this level of visual acuity. One (33%) of three endog¬
five
and neither of two corneal ulcer-related cases recovered 20/400 or better visual acuity. Pseudomonas aeruginosa, the most enous cases
common
gram-negative endophthalmi¬
tis isolate, was associated with a poor visual prognosis, since only one of 12 eyes recovered 20/400 or better vision (Table 4). In contrast to aeruginosa, all four eyes infected with other Pseudomonas species achieved 20/400 or better vision. Other gram-negative cases achieving this level of visual re¬ influenzae (8/10 covery included [80%]) and Proteus species (5/7 [71%]). Eyes that were initially treated with vitrectomy (either three-port pars plana vitrectomy or two-port anterior vitrectomy) and intraocular antibiotics achieved 20/400 or better in 15 (65%) of 23 cases. The eyes that underwent ini¬ tial anterior chamber and/or vitreous aspiration and intraocular antibiotics recovered 20/400 or better vision in 11 (37%) of 30 cases (Table 4). Ten eyes in this series received in¬ traocular dexamethasone phosphate (0.4 mg) together with intraocular anti¬ biotics at the initial treatment. Seven of these patients achieved 20/400 or better visual acuity. Pseudomonas aerugi-
26/53(49.1)
the organism responsible for endophthalmitis in three eyes receiving nosa was
intraocular dexamethasone, and one of these eyes achieved a final visual acuity of 20/300. A repeat injection of intraocular an¬ tibiotics was performed in 24 of the 53 cases in this series (Table 5). Nineteen of these 24 cases had a repeat culture performed, and 14 of these 19 had pos¬ itive culture results. All 14 cases had the same isolate as the original organ¬ ism identified. Eleven of these 14 cases had initial vitreous aspiration and three had initial vitrectomy. Seven of the 24 cases achieved 20/400 or better visual acuity at the last follow-up examination. Persistent infection as manifested by a repeat positive culture occurred in 13% (3/23) of the group with initial vitrec¬ tomy and 37% (11/30) of the group with initial vitreous aspiration. Of the 10 cases receiving intraocular dexametha¬ sone phosphate (0.4 mg), one case had a persistent positive intraocular culture for Serratia marcescens. This case re¬ ceived a repeat injection of intraocular antibiotics and achieved 20/200 visual
acuity. Complications
After Treatment
Because this report is a retrospective chart review, the accurate determina¬ tion of antibiotic toxicity is difficult.
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Prospective fundus photography or fluorescein angiography was not per¬ formed for all patients. However, no description of macular whitening or presumed macular infarction was re¬
corded in the medical record. Retinal detachment was observed within 1 month of the initial treatment in three cases. One eye had successful repair of retinal detachment using pars plana vitrectomy, fluid air exchange, endolaser treatment, and scierai buck¬ ling procedure. The final visual acuity in this eye was 20/70. The remaining two eyes ended with no light perception, with recurrent retinal detachment. COMMENT
Of 336 cases of culture-proven bacte¬ rial endophthalmitis in our laboratory during the 8-year period reviewed, 62 (18.5%) were due to gram-negative iso¬ lates. This percentage is consistent with
recently reported endophthalmitis
se¬
ries from other institutions, in which the incidence of gram-negative endoph¬ thalmitis ranged from 15% to 18%.:!"5 In previous reports from our institution, gram-negative organisms have been cultured in up to 29% of the cases of bacterial endophthalmitis.1,2 Pseudo¬ monas aeruginosa, the most common organism in this report, accounted for 12 (23%) of the 53 cases. This relative frequency of aeruginosa is consistent with a previous report from our institu¬ tion in 1980, in which aeruginosa oc¬ curred in five (22%) of 23 gram-negative endophthalmitis isolates.2 The visual acuity outcomes from aeruginosa endophthalmitis in the current series were poor, since only one of 12 eyes achieved 20/400 or better visual acuity. The one case with a more favorable outcome was a postoperative case ini¬ tially treated with pars plana vitree-
Table 4.—Method of Treatment for
Gram-negative Endophthalmitis Compared Part A
PPV
Organism
With
Specific Organisms Part B
(VA, £20/400) Tap
Ant Vit
PPV
and Final Visual Outcome*
(VA, 20/400* I-
No. Initial Procedure
Culture
Reinjected
No. Recultured
11
24
14 19
Vitrectomy Vitreous aspiration Total
14
The numerator gives the number of eyes with 20/400 the total number of eyes in the category.
tomy and administration of 1 mg of in¬ traocular vancomycin hydrochloride,
0.1 mg of tobramycin, and 0.4 mg of dexamethasone phosphate. This patient achieved a final visual acuity of 20/300. Eight of the remaining 11 eyes pro¬ gressed to no light perception vision, and seven eyes eventually were evis¬ cerated or enucleated. In previous re¬ ports in which final visual acuities were
reported by organism, aeruginosa endophthalmitis has also been associ¬ ated with a poor visual outcome, with five (83%) of six eyes progressing to no light perception visual acuity and the
remaining eye achieving only counting fingers visual acuity.3·5"7 The virulence of aeruginosa in causing severe infections is believed to be multifactoral.8·3 Pseudomonas aeruginosa exists in two forms, a freely
motile form and a microcolony form en¬ cased in a glycocalyx. Organism motility is important in the establishment of infection. In addition, the glycocalyx aeruginosa organism protects the against antibiotic penetration and often prevents phagocytosis. Once estab¬
lished,
aeruginosa produces
a num¬
ber of toxins and proteases that cause host cell destruction and secondarily increase the invasiveness of the organ¬ ism. Finally, aeruginosa does produce ß-lactamase, which renders many com-
or
better visual
Culture
I
Culture
2/3
1/2
1/11 3/14
2/3 3/5
acuity and the denominator gives
monly used antibiotics ineffective against the organism.9 Although aeruginosa is by far the most commonly isolated species of the genus causing infection, other pseudomonads are occasionally oppor¬ tunistic pathogens, and their antimicro¬ bial susceptibility patterns frequently differ from that oî aeruginosa.'3 These Pseudomonas species were isolated in four of our 53 cases. Three of these cases were secondary to penetrat¬ ing ocular trauma, and the remaining case occurred after cataract extraction. All four cases were associated with re¬ covery of useful vision ranging from 20/20 to 20/200. Pseudomonas cepacia was the only organism isolated in this series that was resistant to all of the aminoglycoside antibiotics. In that case,
infrequent
endophthalmitis was diagnosed 12 days after repair of a scierai laceration. Ini¬ tial management included three-port pars plana vitrectomy and intraocular injection of 1 mg of vancomycin hydro¬ chloride and 0.1 mg of gentamicin sul¬ fate. Postoperatively, the intraocular inflammation persisted, and subse¬ quently, after antibiotics sensitivities
intraocular chloramwith clearing of the infection and a return of 20/20 visual were
obtained,
phenicol was injected,
acuity. Haemophilus influenzae was the sec-
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Tap.
needle
53
aspiration of intraocular fluid (all
ond most common organism isolated and accounted for 10 (19%) of the 53 cases. Overall, H influenzae cases achieved 20/400 or better visual acuity in eight (80%) of 10 cases. Haemophilus influenzae was cultured in all three of the cases of secondary intraocular lens in which gram-negative endophthalmi¬ tis developed, and all three recovered vision of 20/400 or better. Six (60%) of the 10 Haemophilus isolates were in conjunctival filtering bleb-associated cases. In bleb-associated Haemophilus endophthalmitis cases, 20/400 or better visual acuity was achieved in four (67%) of six cases. In the largest previously reported study of bleb-associated en¬ dophthalmitis, Mandelbaum and associ¬ ates7 from our institution described H influenzae in seven (70%) of their 10 gram-negative cases. Three cases from this previous report are included in our series of 53 cases. In previous endophthalmitis series from other institutions, Proteus species had been cultured with a frequency ranging from 11% to 40% of the gramnegative isolates.3"5·10 In these reports, Proteus was found most commonly in the acute postoperative setting and was generally associated with a poor visual outcome. Proteus species were isolated in seven (13%) of our 53 cases, and five (71%) of the seven cases recovered vision ranging from 20/30 to 20/200. The relative frequency (Table 1) of the etio¬ logic categories for these cases of gramnegative endophthalmitis does not ap¬ pear significantly different from previous endophthalmitis reports.2·3 In a previous study2 from our institution reporting the etiology of culture-proven bacterial endophthalmitis, 55.9% of cases followed intraocular surgery, 20.5% were in association with conjunc¬ tival filtering blebs, 19.1% occurred af¬ ter trauma, and 4.4% were endogenous.2
Puliafito and associates3 described etio¬
logic categories with similar percentages
in their review of 36 consecutive cases. Nine cases of gram-negative endoph¬ thalmitis following ocular trauma have been described, and three (33%) of these cases achieved 20/400 or better visual acuity.3·5·1114 Proteus mirabilis, K pneumoniae, and the Enterobacter species were generally associated with poorer visual outcomes in these reports. In our series, three (60%) of the five posttraumatic cases recovered 20/400 or better vi¬ sual acuity. The organisms in the current report associated with better vision in¬ cluded cepacia, maltophilia, and stützen. Pseudomonas aeruginosa and Proteus mirabilis, the remaining two isolates from traumatic cases in our se¬ ries, were associated with final visual acuities of no light perception. The enteric gram-negative organ¬ isms are a relatively common cause of endogenous bacterial endophthalmitis. Most reported cases occur in association with urinary or gastrointestinal tract in¬ fection. Escherichia coli endophthalmi¬ tis generally carries a poor visual prog¬ nosis, since no previously reported cases have achieved 20/400 or better visual
acuity.1517 Endogenous endophthalmitis secondary to E coli accounted for three of our 53 cases. One patient with bilateral E coli endophthalmitis retained 20/200 vi¬ sual acuity in one eye while the other eye progressed to no light perception. Both eyes were treated with diagnostic vitre¬ ous aspiration and intraocular antibiot¬ ics; however, there was a 4-day delay in treating the second eye, which pro¬ gressed to no light perception visual acu¬ ity. In another patient with unilateral in-
fection, the final visual acuity was also no light perception. The role of vitrectomy in the treat¬ ment of endophthalmitis is controver¬ sial and is being investigated in the En¬ dophthalmitis Vitrectomy Study.18 Many physicians prefer vitrectomy in the initial treatment of all endoph¬
thalmitis cases, whereas others reserve vitrectomy for the eyes with more se¬ vere inflammation. In this retrospec¬ tive review of gram-negative cases, eyes generally presented with severe inflammation, no view of the posterior pole details, and visual acuity of hand motions or worse. The individual physi¬ cian made the decision to use or not to use vitrectomy in the current series. Although the vitrectomy decision was not based on a prospective protocol, it is interesting to note that 65% (15/23) of the vitrectomy-treated eyes compared with 37% (11/30) of the vitreous aspiration-treated eyes achieved 20/ 400 or better visual acuity. The currently generally recom¬ mended intraocular antibiotic regimen for endophthalmitis includes vancomycin plus an aminoglycoside.19 This com¬ bination provides broad coverage against a broad spectrum of grampositive and gram-negative organisms. The aminoglycosides have been consid¬ ered the drugs of choice for gramnegative infections, and they continue to provide excellent gram-negative cov¬ erage.20 In our series, only one (P cepa¬ cia) of 53 gram-negative isolates dem¬ onstrated in vitro resistance to the aminoglycosides. Despite their efficacy, the routine use of aminoglycosides for endophthalmitis treatment and prophy-
Iaxis has recently been questioned be¬ cause of inconsistent coverage of grampositive organisms and potential retinal toxic reaction.21 Other antibiotics in¬ cluding ceftazidime, ciprofloxacin, and imipenem have been suggested as pos¬ sible alternatives to the aminoglyco¬ sides, and preliminary toxicity reports suggest that these agents may be safe for intraocular injection.2225 Of these al¬ ternatives, our data suggest that ceftazidime may be the most promising, since all gram-negative isolates tested were found to be sensitive to this anti¬ biotic. A clinical report has shown a successful treatment outcome with the use of intraocular vancomycin, ceftazi¬ dime, and dexamethasone.25 We believe that ceftazidime may replace the ami¬ noglycosides as the drug of choice in the treatment and prophylaxis of gram-
negative endophthalmitis. The
use
of intraocular dexametha¬
during the initial treatment of en¬ dophthalmitis in these cases did not ap¬ pear to potentiate the infection or have sone
adverse influence on the final visual result. Seven of 10 eyes receiving in¬ traocular dexamethasone in addition to intraocular antibiotics achieved 20/400 or better vision. Although the data from the current series do not prove a bene¬ ficial effect from the use of intraocular steroids, our clinical impression is that intraocular steroids decrease intraocu¬ lar inflammation and speed visual re¬ covery. We currently administer in¬ traocular dexamethasone phosphate (0.4 mg) together with broad-spectrum intraocular antibiotics in the initial treatment of suspected bacterial en¬ an
dophthalmitis.
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imipenem in vitreous replacement fluid. Ann Ophthalmol. 1987;19:338-339. 25. Stonecipher KG, Parmley VC, Jensen H, Rowsey JJ. Infectious endophthalmitis following sutureless cataract surgery. Arch Ophthalmol. 1991;109:1562-1563.
